I wish to investigate the mechanisms of many proteolytic enzymes including chymotrypsin, elastase, and plasmin. These three were selected because of the wealth of information, including a very striking model system that we have developed, for chymotrypsin; the involvement of elastase in the disease emphysema, and the involvmement of the enzyme plasmin, in cancer. We wish to investigate mechanisms, models and inhibitors of these enzymes. We also wish to investigate the denaturation of immobilized chymotrpysin. We wish to investigate further the norbornane-benzoate ion system which has been proven to have a rate comparable to an enzymatic deacylation. We wish to vary this system to include a crown ether, an ion exchange resin, and an internal carboxylate ion. We also wish to make N-methyl and sulfur instead of oxygen) analogs of this system. We are particularly interested in the development of inhibitors for plasmin, for which we are using inverse substrates. We think we can prevent the carbivorous aspects of proteolytic enzyme deanaturation by immobilizng the enzyme and thus making it sterically impossible for two enzyme molecules to touch one another.